Scavenging Free Iron Reduces Arteriolar Microvasospasms After Experimental Subarachnoid Hemorrhage.

Stroke

Institute for Stroke and Dementia Research (H.L., J.S., N.A.T., K.N., N.P.), University of Munich Medical Center, Ludwig-Maximilians-University (LMU), Germany.

Published: December 2021

Background And Purpose: Subarachnoid hemorrhage (SAH) is associated with acute and delayed cerebral ischemia resulting in high acute mortality and severe chronic neurological deficits. Spasms of the pial and intraparenchymal microcirculation (microvasospasms) contribute to acute cerebral ischemia after SAH; however, the underlying mechanisms remain unknown. We hypothesize that free iron (Fe) released from hemolytic red blood cells into the subarachnoid space may be involved in microvasospasms formation.

Methods: Male C57BL/6 mice (n=8/group) received 200 mg/kg of the iron scavenger deferoxamine or vehicle intravenously and were then subjected to SAH by filament perforation. Microvasospasms of pial and intraparenchymal vessels were imaged three hours after SAH by in vivo 2-photon microscopy.

Results: Microvasospasms occurred in all investigated vessel categories down to the capillary level. Deferoxamine significantly reduced the number of microvasospasms after experimental SAH. The effect was almost exclusively observed in larger pial arterioles (>30 µm) covered with blood.

Conclusions: These results provide proof-of-principle evidence that Fe is involved in the formation of arteriolar microvasospasms after SAH and that arteriolar and capillary microvasospasms are triggered by different mechanisms. Deciphering the mechanisms of Fe-induced microvasospasms may result in novel therapeutic strategies for SAH patients.

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http://dx.doi.org/10.1161/STROKEAHA.120.033472DOI Listing

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Article Synopsis
  • Subarachnoid hemorrhage (SAH) can lead to cerebral ischemia, and recent research suggests that microvasospasm, influenced by perivascular inflammation, plays a role in this condition.
  • A mouse model with intravital 2-photon imaging was used to study vascular and perivascular changes following SAH, revealing that neutrophils and neutrophil extracellular traps (NETs) contribute to the development of microvasospasms.
  • The findings indicate that targeting perivascular NETs could be a potential new treatment approach for mitigating microvasospasm-related issues in SAH.
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Background: Subarachnoid hemorrhage (SAH) is characterized by acute and delayed reductions of cerebral blood flow (CBF) caused, among others, by spasms of cerebral arteries and arterioles. Recently, the inactivation of perivascular macrophages (PVM) has been demonstrated to improve neurological outcomes after experimental SAH, but the underlying mechanisms of protection remain unclear. The aim of our exploratory study was, therefore, to investigate the role of PVM in the formation of acute microvasospasms after experimental SAH.

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Perfusion pressure determines vascular integrity and histomorphological quality following perfusion fixation of the brain.

J Neurosci Methods

April 2022

Institute for Stroke and Dementia Research (ISD), Ludwig-Maximilians-University (LMU), Munich Medical Center, Munich, Germany; Cluster for Systems Neurology (SyNergy), Munich, Germany. Electronic address:

Introduction: Histology on fixed brain tissue is a key technique to investigate the pathophysiology of neurological disorders. Best results are obtained by perfusion fixation, however, multiple protocols are available and so far the optimal perfusion pressure (PP) for the preservation of brain tissue while also maintaining vascular integrity is not defined. Therefore, the aim of our study was to investigate the effect of different PPs on the cerebral vasculature and to define the PP optimal for the preservation of both vascular integrity and tissue fixation.

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Scavenging Free Iron Reduces Arteriolar Microvasospasms After Experimental Subarachnoid Hemorrhage.

Stroke

December 2021

Institute for Stroke and Dementia Research (H.L., J.S., N.A.T., K.N., N.P.), University of Munich Medical Center, Ludwig-Maximilians-University (LMU), Germany.

Background And Purpose: Subarachnoid hemorrhage (SAH) is associated with acute and delayed cerebral ischemia resulting in high acute mortality and severe chronic neurological deficits. Spasms of the pial and intraparenchymal microcirculation (microvasospasms) contribute to acute cerebral ischemia after SAH; however, the underlying mechanisms remain unknown. We hypothesize that free iron (Fe) released from hemolytic red blood cells into the subarachnoid space may be involved in microvasospasms formation.

View Article and Find Full Text PDF

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